Alberge Jean-Baptiste, Dutta Ankit K, Poletti Andrea, Coorens Tim H H, Lightbody Elizabeth D, Toenges Rosa, Loinaz Xavi, Wallin Sofia, Dunford Andrew, Priebe Oliver, Dagan Johnathan, Boehner Cody J, Horowitz Erica, Su Nang K, Barr Hadley, Hevenor Laura, Towle Katherine, Beesam Rashmika, Beckwith Jenna B, Perry Jacqueline, Cordas Dos Santos David M, Bertamini Luca, Greipp Patricia T, Kübler Kirsten, Arndt Peter F, Terragna Carolina, Zamagni Elena, Boyle Eileen M, Yong Kwee, Morgan Gareth, Walker Brian A, Dimopoulos Meletios Athanasios, Kastritis Efstathios, Hess Julian, Sklavenitis-Pistofidis Romanos, Stewart Chip, Getz Gad, Ghobrial Irene M
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Department of Medicine, Harvard Medical School, Boston, MA, USA.
Nat Genet. 2025 May 21. doi: 10.1038/s41588-025-02196-0.
Reliable strategies to capture patients at risk of progression from precursor stages of multiple myeloma (MM) to overt disease are still missing. We assembled a comprehensive collection of MM genomic data comprising 1,030 patients (218 with precursor conditions) that we used to identify recurrent coding and non-coding candidate drivers as well as significant hotspots of structural variation. We used those drivers to define and validate a simple 'MM-like' score, which we could use to place patients' tumors on a gradual axis of progression toward active disease. Our MM precursor genomic map provides insights into the time of initiation and cell-of-origin of the disease, order of acquisition of genomic alterations and mutational processes found across the stages of transformation. Taken together, we highlight here the potential of genome sequencing to better inform risk assessment and monitoring of MM precursor conditions.
目前仍缺乏可靠的策略来识别处于从多发性骨髓瘤（MM）前驱阶段进展为显性疾病风险中的患者。我们收集了一个全面的MM基因组数据集，包括1030名患者（218名处于前驱状态），用于识别反复出现的编码和非编码候选驱动基因以及结构变异的重要热点区域。我们利用这些驱动基因定义并验证了一个简单的“MM样”评分，可用于将患者的肿瘤置于向活动性疾病进展的渐进轴上。我们的MM前驱基因组图谱为疾病的起始时间、起源细胞、基因组改变的获得顺序以及在转化各阶段发现的突变过程提供了见解。总之，我们在此强调基因组测序在更好地指导MM前驱状态的风险评估和监测方面的潜力。
